The aim of this program project is the interdisciplinary study of the interactions of neurotropic viruses with the nervous system and the resultant injury and alteration of nervous system function that occurs. Four viral systems have been chosen for study because they share two important features: (1) They interact with the nervous system in a unique way and thus cause specific injury and alteration of nervous system function; (2) The molecular biology and genetics of these viruses is well characterized, thus allowing one to identify the viral genes (and gene products) responsible for the specificity of their interaction with the nervous system. The program project will not only focus on viral factors responsible for nervous system injury, but will study host factors which affect the manner in which these viruses interact with the nervous system. The viruses to be studied are: reovirus, herpes virus, polio virus, and vesicular stomatitis virus. One major area of study will be the effect of various genetic alterations in neurotropic viruses and how these changes affect the interaction of a neurotropic virus with the central nervous system. A second major area will be the interaction of neurotropic viruses with specific receptors in the nervous system and the immune system. In vivo and in vitro approaches will be employed utilizing animals of varying developmental ages and with specific genetic mutations of the nervous system and b) a wide variety of primary and continuous central and peripheral nervous tissue cultures. Extensive collaboration will occur between the six investigators on the program project involving the following interdisciplinary areas: Viral genetics and molecular biology, neuropathology, neuropharmacology, neurophysiology, neuroimmunology, and developmental neurobiology.